J Neurosurg. 2014 Oct 24:1-9. [Epub ahead of print]
Increases in microvascular perfusion and tissue oxygenation via pulsed electromagnetic fields in the healthy rat brain.
Bragin DE1, Statom GL, Hagberg S, Nemoto EM.
- 1Department of Neurosurgery and.
OBJECT High-frequency pulsed electromagnetic field stimulation is an emerging noninvasive therapy being used clinically to facilitate bone and cutaneous wound healing. Although the mechanisms of action of pulsed electromagnetic fields (PEMF) are unknown, some studies suggest that its effects are mediated by increased nitric oxide (NO), a well-known vasodilator. The authors hypothesized that in the brain, PEMF increase NO, which induces vasodilation, enhances microvascular perfusion and tissue oxygenation, and may be a useful adjunct therapy in stroke and traumatic brain injury. To test this hypothesis, they studied the effect of PEMF on a healthy rat brain with and without NO synthase (NOS) inhibition.
METHODS In vivo two-photon laser scanning microscopy (2PLSM) was used on the parietal cortex of rat brains to measure microvascular tone and red blood cell (RBC) flow velocity in microvessels with diameters ranging from 3 to 50 μm, which includes capillaries, arterioles, and venules. Tissue oxygenation (reduced nicotinamide adenine dinucleotide [NADH] fluorescence) was also measured before and for 3 hours after PEMF treatment using the FDA-cleared SofPulse device (Ivivi Health Sciences, LLC). To test NO involvement, the NOS inhibitor NG-nitro-l-arginine methyl ester (L-NAME) was intravenously injected (10 mg/kg). In a time control group, PEMF were not used. Doppler flux (0.8-mm probe diameter), brain and rectal temperatures, arterial blood pressure, blood gases, hematocrit, and electrolytes were monitored.
RESULTS Pulsed electromagnetic field stimulation significantly dilated cerebral arterioles from a baseline average diameter of 26.4 ± 0.84 μm to 29.1 ± 0.91 μm (11 rats, p < 0.01). Increased blood volume flow through dilated arterioles enhanced capillary flow with an average increase in RBC flow velocity by 5.5% ± 1.3% (p < 0.01). Enhanced microvascular flow increased tissue oxygenation as reflected by a decrease in NADH autofluorescence to 94.7% ± 1.6% of baseline (p < 0.05). Nitric oxide synthase inhibition by L-NAME prevented PEMF-induced changes in arteriolar diameter, microvascular perfusion, and tissue oxygenation (7 rats). No changes in measured parameters were observed throughout the study in the untreated time controls (5 rats).
CONCLUSIONS This is the first demonstration of the acute effects of PEMF on cerebral cortical microvascular perfusion and metabolism. Thirty minutes of PEMF treatment induced cerebral arteriolar dilation leading to an increase in microvascular blood flow and tissue oxygenation that persisted for at least 3 hours. The effects of PEMF were mediated by NO, as we have shown in NOS inhibition experiments. These results suggest that PEMF may be an effective treatment for patients after traumatic or ischemic brain injury. Studies on the effect of PEMF on the injured brain are in progress.
2PLSM = two-photon laser scanning microscopy; L-NAME = NG-nitro-l-arginine methyl ester; NADH; NADH = nicotinamide adenine dinucleotide; NO = nitric oxide; NOS = NO synthase; PEMF = pulsed electromagnetic field(s); RBC = red blood cell; brain metabolism; cerebrovascular flow; pulsed electromagnetic field; two-photon laser scanning microscopy; vasodilation
Bioelectromagnetics. 2003;Suppl 6:S107-47.
Microwave effects on the nervous system.
D’Andrea JA, Chou CK, Johnston SA, Adair ER.
Naval Health Research Center Detachment, Brooks City-Base, TX 78235-5365, USA. firstname.lastname@example.org
Studies have evaluated the electroencephalography (EEG) of humans and laboratory animals during and after Radiofrequency (RF) exposures. Effects of RF exposure on the blood-brain barrier (BBB) have been generally accepted for exposures that are thermalizing. Low level exposures that report alterations of the BBB remain controversial. Exposure to high levels of RF energy can damage the structure and function of the nervous system. Much research has focused on the neurochemistry of the brain and the reported effects of RF exposure. Research with isolated brain tissue has provided new results that do not seem to rely on thermal mechanisms. Studies of individuals who are reported to be sensitive to electric and magnetic fields are discussed. In this review of the literature, it is difficult to draw conclusions concerning hazards to human health. The many exposure parameters such as frequency, orientation, modulation, power density, and duration of exposure make direct comparison of many experiments difficult. At high exposure power densities, thermal effects are prevalent and can lead to adverse consequences. At lower levels of exposure biological effects may still occur but thermal mechanisms are not ruled out. It is concluded that the diverse methods and experimental designs as well as lack of replication of many seemingly important studies prevents formation of definite conclusions concerning hazardous nervous system health effects from RF exposure. The only firm conclusion that may be drawn is the potential for hazardous thermal consequences of high power RF exposure.
Bioelectromagnetics. 2003;Suppl 6:S39-62.
Behavioral and cognitive effects of microwave exposure.
D’Andrea JA, Adair ER, de Lorge JO.
Naval Health Research Center Detachment, Brooks City-Base, Texas, USA.
This paper presents an overview of the recent behavioral literature concerning microwave exposure and discusses behavioral effects that have supported past exposure standards. Other effects, which are based on lower levels of exposure, are discussed as well, relative to setting exposure standards. The paper begins with a brief discussion of the ways in which behavioral end points are investigated in the laboratory, together with some of the methodological considerations pertinent to such studies when radio frequency (RF) exposure is involved. It has been pointed out by several sources that exposure to RF radiation can lead to changes in the behavior of humans and laboratory animals that can range from the perceptions of warmth and sound to lethal body temperatures. Behavior of laboratory animals can be perturbed and, under certain other conditions, animals will escape and subsequently avoid RF fields; but they will also work to obtain a burst of RF energy when they are cold. Reports of change of cognitive function (memory and learning) in humans and laboratory animals are in the scientific literature. Mostly, these are thermally mediated effects, but other low level effects are not so easily explained by thermal mechanisms. The phenomenon of behavioral disruption by microwave exposure, an operationally defined rate decrease (or rate increase), has served as the basis for human exposure guidelines since the early 1980s and still appears to be a very sensitive RF bioeffect. Nearly all evidence relates this phenomenon to the generation of heat in the tissues and reinforces the conclusion that behavioral changes observed in RF exposed animals are thermally mediated. Such behavioral alteration has been demonstrated in a variety of animal species and under several different conditions of RF exposure. Thermally based effects can clearly be hazardous to the organism and continue to be the best predictor of hazard for homosapiens. Nevertheless, similar research with man has not been conducted. Although some studies on human perception of RF exist, these should be expanded to include a variety of RF parameters.
Lik Sprava. 1992 Oct;(10):69-71.
The brain function of animals exposed to the action of centimeter electromagnetic waves.
[Article in Russian]
Smolia AL, Bezdol’naia IS.
It was established that centimeter electromagnetic waves (EMW) are a biologically active factor. Dynamic of changes of behavioural reactions under the effect of EMW evidences instability of the functional state of the brain EMW densities of 1000, 1500 mW/cm2 produce a response characterized by inhibition of motor activity.
Health Phys. 1991 Jul;61(1):29-40.
Microwave radiation absorption: behavioral effects.
Naval Aerospace Medical Research Laboratory, Naval Air Station, Pensacola, FL 32508-5700.
The literature contains much evidence that absorption of microwave energy will lead to behavioral changes in man and laboratory animals. The changes include simple perturbations or outright stoppage of ongoing behavior. On one extreme, intense microwave absorption can result in seizures followed by death. On the other extreme, man and animals can hear microwave pulses at very low rates of absorption. Under certain conditions of exposure, animals will avoid microwaves, while under other conditions, they will actively work to obtain warmth produced by microwaves. Some research has shown behavioral effects during chronic exposure to low-level microwaves. The specific absorption rates that produce behavioral effects seem to depend on microwave frequency, but controversy exists over thresholds and mechanism of action. In all cases, however, the behavioral disruptions cease when chronic microwave exposure is terminated. Thermal changes in man and animals during microwave exposure appear to account for all reported behavioral effects.
Int J Radiat Biol Relat Stud Phys Chem Med. 1986 Nov;50(5):761-87.
The effects of low-level radiofrequency and microwave radiation on brain tissue and animal behaviour.
Blackwell RP, Saunders RD.
There has been much public interest and controversy about the effects of exposure to low levels of microwave and radiofrequency radiation. Of particular interest are reports of radiation-induced changes in brain tissue and animal behaviour. This review considers the evidence supporting some of these effects. The main conclusions of the review are: The levels of tracer substances in the brain tissue of conscious or anaesthetized animals can be altered by acute exposure to microwave radiation that is sufficient to raise the brain temperature by several degrees Celsius. However, the results of such experiments are difficult to interpret, being in some cases contradictory or influenced by various confounding factors, and the data cannot be considered sufficient to recommend a threshold for human tolerance. The evidence that calcium ion exchange in living nervous tissues is affected by amplitude-modulated radiofrequency and microwave radiation is inconclusive. Exposure sufficient to cause an increase in core temperature of about 1 degree C, corresponding to specific energy absorption rates of about 2-8 W kg-1 may adversely affect animal behaviour.
Effects of continuous-wave, pulsed, and sinusoidal-amplitude-modulated microwaves on brain energy metabolism.
Sanders AP, Joines WT, Allis JW.
A comparison of the effects of continuous-wave, sinusoidal-amplitude-modulated, and pulsed square-wave-modulated 591-MHz microwave exposures on brain energy metabolism was made in male Sprague-Dawley rats (175-225 g). Brain NADH fluorescence, adenosine triphosphate (ATP) concentration, and creatine phosphate (CP) concentration were determined as a function of modulation frequency. Brain temperatures of animals were maintained between -0.1 and -0.4 degrees C from the preexposure temperature when subjected to as much as 20 mW/cm2 (average power) CW, pulsed, or sinusoidal-amplitude modulated 591-MHz radiation for 5 min. Sinusoidal-amplitude-modulated exposures at 16-24 Hz showed a trend toward preferential modulation frequency response in inducing an increase in brain NADH fluorescence. The pulse-modulated and sinusoidal-amplitude-modulated (16 Hz) microwaves were not significantly different from CW exposures in inducing increased brain NADH fluorescence and decreased ATP and CP concentrations. When the pulse-modulation frequency was decreased from 500 to 250 pulses per second the average incident power density threshold for inducing an increase in brain NADH fluorescence increased by a factor of 4–ie, from about 0.45 to about 1.85 mW/cm2. Since brain temperature did not increase, the microwave-induced increase in brain NADH and decrease in ATP and CP concentrations was not due to hyperthermia. This suggests a direct interaction mechanism and is consistent with the hypothesis of microwave inhibition of mitochondrial electron transport chain function of ATP production.
The differential effects of 200, 591, and 2,450 MHz radiation on rat brain energy metabolism.
Sanders AP, Joines WT, Allis JW.
Three key compounds in brain energy metabolism have been measured during and after exposure to continuous wave radiofrequency radiation at 200, 591, and 2,450 MHz. Frequency-dependent changes have been found for all three compounds. Changes in NADH fluorescence have been measured on the surface of a surgically uncovered rat brain during exposure. At 200 and 591 MHz, NADH fluorescence increased in a dose-dependent manner between approximately 1 and 10 mW/cm2, then became constant at higher exposures. There was no effect at 2,450 MHz. Levels of ATP and CP were measured in whole brain after exposure. The ATP levels were decreased at 200 and 591 MHz but not at 2,450 MHz. The CP levels decreased only at 591 MHz. The effect of duration of exposure (up to 5 min) was investigated for all compounds at 200 MHz and 2,450 MHz, and exposures to 20 minutes were examined at 591 MHz. Temperature in the rat brain was essentially constant for all exposures. A general mechanism for inhibition of the mitochondrial electron transport chain and the CP-kinase reaction pathway by radiofrequency radiation has been proposed.
Neurobehav Toxicol. 1980 Spring;2(1):49-58.
Behavioral effects of microwaves.
Microwaves can produce sensations of warmth and sound in humans. In other species, they also can serve as cues, they may be avoided, and they can disrupt ongoing behavior. These actions appear to be due to heat produced by energy absorption. The rate of absorption depends on the microwave parameters and the electrical and geometric properties of the subject. We, therefore, cannot predict the human response to microwaves based on data from other animals without appropriate scaling considerations. At low levels of exposure, microwaves can produce changes in behavior without large, or even measureable, changes in body temperature. Thermoregulatory behavior may respond to those low levels of heat, and thereby affect other behavior occurring concurrently. There are no data that demonstrate that behavioral effects of microwaves depend on any mechanism other than reactions to heat. Our interpretation of whether a reported behavioral effect indicates that microwaves may be hazardous depends on our having a complete description of the experiment and on our criteria of behavioral toxicity.
Physiol Chem Phys. 1978;10(5):387-98.
Low power radio-frequency and microwave effects on human electroencephalogram and behavior.
In a pilot study of ten human subjects, temporary changes in brain waves and behavior were seen on exposure to power densities lower than 10(-12) W/cm2, which is substantially below typical urban levels. Frequencies included .1 to 960 MHz continuous and 8.5 to 9.6 GHz pulse-modulated waves. Since the relaxation frequency of protein-bound water is considered to fall between 100 and 1,000 MHz, absorptions and quantum effects may be the mechanistic basis for the electroencephalogram changes observed in most of the subjects produced by 10(-15) W/cm2 cw radio-frequency energy of between 130 and 960 MHz. Constructive and destructive interference patterns from standing waves within the skull possibly interact with the bioelectric generators in the brain, since electroencephalogram wave amplitudes and frequencies increased or decreased respectively at different radio wavelengths.